rs199422262

Positions:

• chr3-169765013-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NR_001566.1(TERC):​n.48A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TERC NR_001566.1 non_coding_transcript_exon
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.92

Genes affected

Telomerase-vert (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-169765013-T-C is Pathogenic according to our data. Variant chr3-169765013-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 39297.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-169765013-T-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERC	NR_001566.1	n.48A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
Telomerase-vert	ENST00000363312.1	n.35A>G		non_coding_transcript_exon_variant	1/1	6
TERC	ENST00000602385.1	n.48A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dyskeratosis congenita, autosomal dominant 1 Pathogenic:1

Pathogenic, no assertion criteria provided

curation

GeneReviews

May 10, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.65
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199422262; hg19: chr3-169482801;